We have been studying the effects of cancer growth on the deposition, mobilization, and metabolism of body fat in an attempt to understand cancer-induced cachexia. We have developed new techniques for studying the esterification of fatty acids by selected adipose tissue sites in vivo. The method involves the direct injection of radioactive fatty acids into the interstitial fluid of the fat pad and subsequent measurements of the incorporation of the tracer into di-\and triacylglycerol. In addition there are measurements of movement of the tracer into the circulation, subsequent turnover of the labeled triacylglycerol in the fat pads, and measurement of expired radioactive carbon dioxide and pool sizes of free fatty acids in extracellular and intracellular compartments of the adipose tissue in control and tumor-bearing (Ehrlich ascites tumor) mice. The data have been analyzed by multicompartmental analysis. Our studies show that there is a dramatic increase in the size of the adipose tissue free fatty acid compartment during tumor growth, coupled with a highly significant decrease in the rate of esterification of added free fatty acids into triacylglycerol. This defect could account in large part for the loss of body fat. Moreover, the accumulation of free fatty acids in the adipose tissue could result in the inhibition of other lipogenic processes (lipoprotein lipase activity, fatty acid synthesis) in cancer-bearing mice. The studies are continuing and being extended to mice with another form of carcinoma (virus-induced thymomas and lymphomas) in AKR mice which are known to develop lymphomas spontaneously. Studies of fatty acid oxidation in liver mitochondria of tumor-bearing mice indicate this process is severely inhibited; experiments are in progress to establish whether or not this represents increased mitochondrial fragility or whether fatty acid oxidation is inhibited in intact liver of tumor-bearing mice as well. Finally, studies of the effects of lipid mobilizing factors derived from both types of tumor-bearing mice (described above) on the turnover and oxidation of adipose tissue triacylglycerol fatty acids are continuing. (N)